Anal human papillomavirus DNA screening by Hybrid Capture II in human immunodeficiency virus-positive patients with or without anal intercourse

High risk human papillomaviruses (HPVs) have emerged as risk factors for anal carcinoma, of which incidence is higher in HIV-positive patients than in the general population. The aim of our study was to investigate the prevalence and risk factors for anal HPV infections in HIV-positive patients with or without history of anal intercourse. Fifty HIV 1-infected patients (36 men and 14 women) were tested at entry and followed-up every 3 months for one year for the presence of anal HPV DNA by the Hybrid Capture II trade mark assay. A series of 50 HIV-negative subjects matched for age and sex served as controls. At enrollment, anal HPV DNA was present in 29/50 HIV-positive patients (58 %) and in 3/50 control subjects (6 %). High risk (HR) HPV genotypes were detected in 20/50 HIV-positive patients (40 %) with no difference in homosexual men and other HIV-positive patients. Risk factors for HPV infection were CD4 + cell counts less than 500/microL (RR: 2.13 [95 % CI: 1.0-4.7]) and history of anogenital warts (RR: 2.36 [95 % CI: 1.2-4.6]). The HPV load was higher in patients with CD4+ < or = 500/microL than in patients with CD4 + > 500/microL (p < 0.04). During the follow-up, anal HR HPV DNA was repeatedly identified at high levels in 5 HIV-positive patients. There is some convincing evidence that HIV-positive patients with low CD4+ cells, whatever the routes of HIV transmission, have a high rate of anal HPV infection and might be at increased risk of developing anal neoplastic lesions. Identifying HR HPV infection might be warranted in immunosuppressed patients.     

P16和Ki-67检测在鉴定女性外阴上皮内瘤样病变分级中的价值

目的观察P16和Ki-67在正常外阴组织和不同级别女性外阴上皮内瘤样病变(VIN)组织中的表达,探讨二者在鉴别高级别VIN中的价值。方法收集76例女性外阴组织,其中35例无VIN,13例低级别VIN、28例高级别VIN,均采用免疫组化Envision法进行标记。结果正常上皮、低级别VIN和高级别VIN病例P16的阳性率分别是8.57%,23.08%和92.86%;Ki-67的阳性率分别为5.71%,38.46%和96.43%;在高级别VIN中P16和Ki-67的表达和正常组及低级别VIN之间的阳性率比较,差异均有显著性意义(P均<0.001)。作为鉴别高级别VIN标记物P16和Ki-67的敏感性分别是92.86%和96.43%,特异性分别是93.75%和87.50%。结论P16和Ki-67在外阴上皮正常组、低级别上皮内瘤、高级别上皮内瘤中敏感性较高。采用二者联合标记,能有效降低假阳性率。     

Prevalence, Incidence, and Risk Factors for Human Papillomavirus 16 Seropositivity in Australian Homosexual Men

BACKGROUND:: Human papillomavirus 16 (HPV16) has been causally associated with approximately 70% of anal cancers. This cancer is markedly increasing among homosexual men. There is limited knowledge of the epidemiology and natural history of anal HPV infection in homosexual men. METHODS:: Behavioral data and sera for antibodies to HPV16 L1 were collected annually for 1427 HIV-negative and 245 HIV-positive Australian homosexual men. Seroprevalence, seroincidence, and risk factors were calculated. RESULTS:: Among HIV-negative men, 25.4% were HPV16 seropositive at baseline compared with 44.3% of HIV-positive men. HPV16 seroincidence was 3.1/100 person-years among HIV-negative men and 1.3/100 person-years among HIV-positive men. Seroincidence among HIV-negative men remained >3% per year until 45 years of age, before declining. In multivariate analyses of data from HIV-negative men, seroprevalent HPV16 was associated with sexual risk behaviors and seropositivity for several viral sexually transmissible infections. Seroincident HPV16 was associated with younger age and unprotected anal intercourse with HIV-positive partners. Among men who predominantly practiced insertive anal intercourse, circumcision was associated with a 57% reduction in seroincident HPV16 (hazard ratio = 0.43, 95% confidence interval: 0.21-0.88, P = 0.021). CONCLUSIONS:: HPV16 seroincidence remained common in men until their mid 40s suggesting that vaccination may be protective in sexually active young gay men. Both HPV16 seroprevalence and seroincidence correlated well with markers of higher risk sexual activity, particularly receptive anal sexual practices. An association between circumcision and decreased HPV16 seroconversion in HIV-negative men who preferred the insertive position in anal sex was observed.     

Human papillomavirus (HPV) viral load and HPV type in the clinical outcome of HIV-positive patients treated with imiquimod for anogenital warts and anal intraepithelial neoplasia

OBJECTIVE: To evaluate the efficacy of 5% imiquimod in HIV-positive male patients with anogenital warts or anal intraepithelial neoplasia (AIN), and to elucidate whether human papillomavirus (HPV) type and viral load were important for clinical outcome and recurrences. METHODS: Thirty-seven patients with histologically proven anogenital warts or AIN were enrolled. Topical 5% imiquimod was applied three times per week for more than 8 h overnight for 16 weeks, although patients were allowed to continue therapy for 4 more weeks if they did not have complete clearance of lesions. RESULTS: Mean age was 34 years. The perianal area was the main lesion location. Thirty-three patients had CD4 counts of < 500 cells/mm(3). Eighteen patients had a histopathological diagnosis of AIN-1. Main HPV types detected corresponded to low-risk HPV types. At 20 weeks of therapy, 46% patients achieved total clearance whereas 14 patients had > 50% clearance. Recurrence was observed in 5 of 17 patients who cleared. Clearance was not influenced by patients' CD4 counts, wart location, HIV viral load or HPV viral load. CONCLUSIONS: The assumption that visible perianal warts are benign lesions in HIV-positive patients has to be reevaluated since an important number of such lesions could correspond to low-grade anal disease, which in turn could progress to high-grade anal disease or cancer. In addition, our results in this preliminary study indicate that imiquimod appears to be effective in treating AIN in HIV-positive patients. Further studies are needed to document its utility to prevent high-grade dysplasia and/or anal cancer.     

外阴恶性肿瘤中P21~(WAF1/CIP1) P53及HPV6/11 HPV16/18的检测和意义

目的　探讨P2 1WAF1/CIP1,P5 3及HPV6/11,16/18与外阴恶性肿瘤的关系。方法　P2 1WAF1/CIP1,P5 3用免疫组化SP法检测 ;HPV6/11,16/18用原位杂交法 (ISH)检测。结果　P2 1WAF1/CIP1,P5 3在外阴恶性肿瘤组、外阴上皮内瘤变 (VIN)组、正常对照组中的阳性检测率分别为 40 .0 0 % (12 /3 0 )、63 .3 3 % (19/3 0 ) ,5 2 .3 8% (11/2 1) ,47.62 % (10 /2 1) ,0 (0 /10 )和 0 (0 /10 ) ;外阴病变各组P2 1WAF1/CIP1,P5 3与正常组比较差异均有显著性 (P均 <0 .0 5 ) ;HPV6/11、16/18在外阴恶性肿瘤组、VIN组中的阳性检测率分别为 60 .0 0 % (18/3 0 )和 3 3 .3 3 % (10 /3 0 ) ,42 .86% (9/2 1)和 2 8.5 7% (6/2 1) ,正常对照组没有检测出 ;HPV 6/11阳性率外阴恶性肿瘤组、VIN组与正常组比较差异均有显著性 (P均 <0 .0 5 ) ;外阴恶性肿瘤组HPV16/18阳性率与正常组比较差异有显著性 (P <0 .0 5 )。结论　P2 1WAF1/CIP1P5 3及HPV感染在外阴恶性肿瘤的发生发展中可能起一定的作用     

HPV-associated intraepithelial neoplasia of external genitalia

Intraepithelial neoplasia of the external genitalia with the histologic features, but not the clinical characteristics, of Bowen's disease, has been described under several names: bowenoid papulosis (BP) of the penis or genitalia,^1,2 pigmented penile papules with carcinoma in situ changes,³ multicentric pigmented Bowen's disease (MPBD),^4,5 multicentric Bowen's disease of the genitalia,⁶ reversible vulvar atypia,⁷ bowenoid atypia of the vulva,⁸ bowenoid dysplasia of the vulva,⁹ early vulvar carcinoma,¹⁰ vulvar neoplasia in the young,¹¹ vulvar intraepithelial neoplasia (VIN),¹² penile intraepithelial neoplasia,¹³ carcinoma in situ of the vulva,¹⁴ multicentric vulvar carcinoma in situ,¹⁵ and intraepithelial carcinoma of the vulva.¹⁶

The term bowenoid papulosis of the penis is adequate, since it stresses the multifocal and papular type of the lesions, their localization, and histologic pattern. The term multicentric pigmented Bowen's disease is suitable for the confluent, usually heavily pigmented, and somewhat proliferative lesions in women. The relationship between BP or MPBD and Bowen's disease is currently substantiated by the detection of the same type of human papillomavirus (HPV) in lesions recognized as BP or MPBD, and in typical cases of genital Bowen's disease ¹⁷ (Obalek S, et al. unpublished observations).     

Medical and surgical approaches to vulvar intraepithelial neoplasia

Vulvar intraepithelial neoplasia (VIN) is a precursor to invasive vulvar carcinoma. The two major types of VIN, usual and differentiated, differ in epidemiology, pathogenesis, clinical manifestations, pathology, and malignant potential. Usual VIN commonly occurs in younger women. It is associated with human papillomavirus and tends to have multifocal and multicentric involvement. Differentiated VIN is frequently associated with benign vulvar dermatoses such as lichen sclerosus and lichen simplex chronicus. It occurs in older women and typically is unifocal and unicentric. Clinicians must have a high suspicion for VIN, which is diagnosed by biopsy. Surgical excision has been the standard treatment in order to prevent progression to invasive disease. The objectives of treatment have expanded to include preservation of normal vulvar function and anatomy. Therefore, management options are being investigated, including topical therapy, laser excision and vaporization, and photodynamic therapy. All can be effective in both eliminating disease and maintaining relatively normal‐appearing and functioning anatomy.     

Human papillomavirus-associated induction of human β-defensins in anal intraepithelial neoplasia

Background  Antimicrobial peptides and proteins (AMPs) are widely distributed effector molecules of the innate immune system with well-known antibacterial activity. However, there is a paucity of information regarding antiviral effects of AMPs.
Objectives  The present study was performed to analyse expression of AMPs in human papillomavirus (HPV)-associated anal skin lesions of human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), a special high-risk group for persistent HPV infections and anal dysplasia.
Methods  Skin lesions were analysed for the presence of LL-37, RNase 7, and human β-defensin (hBD)-1, hBD-2 and hBD-3. Moreover, HPV typing and HPV DNA load determination for HPV types 6, 11, 16, 18, 31 and 33 were performed to evaluate possible correlations between expression of AMPs and lesional HPV types.
Results  Skin biopsies of 45 HIV-positive MSM with anal intraepithelial neoplasia (AIN), anal condylomata acuminata or unaffected anal mucosa, as well as condylomata acuminata of eight HIV-negative MSM, were analysed for AMP mRNA expression. Additionally, immunohistochemical analysis for hBD-2 and hBD-3 was performed in a total of 45 samples. hBD-2 and hBD-3 gene and protein expression was significantly increased in both AIN and condyloma, whereas LL-37, RNase 7 and hBD-1 gene expression did not differ significantly from unaffected anal mucosa. AMP expression correlated neither with the number of HPV types nor with the high-risk and low-risk HPV DNA loads of the quantified types. No significant differences in AMP expression were observed in condylomata of HIV-positive and HIV-negative MSM.
Conclusions  hBD-2 and hBD-3 expression was shown to be significantly upregulated in HPV-associated anal skin lesions of both HIV-positive and HIV-negative MSM. Their biological significance in the innate immunity against these lesions needs further research.     

CD4+ T lymphocytopenia with disseminated HPV

BACKGROUND: There have been several reports of HIV-negative patients with chronic idiopathic CD4+ T lymphocytopenia, the diagnostic criteria for which are: depressed numbers of circulating T lymphocytes (less than 300/ micro l or less than 20%) on more than one occasion; no laboratory evidence of HIV-1 or HIV-2 infection; and the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4+ T lymphocytes. METHODS: We report a patient with disseminated human papillomavirus infection associated with idiopathic CD4+ T-cell lymphocytopenia. A 50-year-old woman presented to the dermatology clinic with a 10-year history of widespread verrucae involving the skin and the cervix. RESULTS: Biopsy from the arm revealed a common wart. PCR analysis performed from the paraffin-embedded block was strongly positive for HPV type 2. Other HPV types (including EV-associated HPV 5, 8, 14, 15, 17) were not found. Further laboratory work up revealed T-cell lymphocytopenia, with an absolute CD4 count of 21. HIV tests were repeatedly negative. She was treated with interferon A 8 million units SQ three times per week with partial improvement. The patient underwent a hysterectomy for cervical dysplasia and a vulvectomy for vulvar intraepithelial neoplasia. She developed small-cell lung carcinoma and died. CONCLUSIONS: The diagnosis of idiopathic CD4+ T-cell lymphocytopenia should be considered in any patient with widespread viral, fungal, or mycobacterial infection whose HIV test is negative, and appropriate evaluation of the absolute CD4+ counts should be performed.     

'HPV vulvitis' revisited: frequent and persistent detection of novel epidermodysplasia verruciformis-associated HPV genotypes

Background:  'Human papillomavirus (HPV) vulvitis' is a disputed entity where most studies examining for genital-mucosal (GM) HPV have been negative.
Methods:  Using degenerate and type specific primers for cutaneous (CU), GM and epidermodysplasia verruciformis (EV) HPV types, the prevalence of specific HPV types was investigated in biopsy specimens from 19 women with 'HPV vulvitis', seven with asymptomatic vulvar squamous papillomatosis (ASxVSP), and controls of vulvar fibroepithelial polyps (FEP) (15), vulvar condyloma (10) and normal vulva (NV) (10).
Results:  HPV DNA/EV HPV/GM HPV/CU HPV were detected in 84/74/47/5% of vulvitis patients, 78/71/0/28% of ASxVSP, 47/20/20/7% of FEP, 10/10%/0/0 of NV and 100/0/100/10% of condyloma. Fourteen putatively novel HPV genotypes were detected in vulvitis and ASxVSP patients, but not in controls. The two most frequent novel EV HPV, Alb-4 and DL285, were detected in 9/19 (47%) and 5/19 (26%) of vulvitis cases and were persistently identified in serial biopsies. HPV co-infection and Alb-4 infection occurred significantly more frequently in vulvitis patients, particularly those complaining of 'burning' (62/62% vs. 17/7%, p ≤ 0.004). Koilocytosis was identified significantly more frequently in vulvitis compared with non-condyloma controls (81% vs. 40%, p = 0.0001), and its presence correlated with detection of HPV DNA (r = 0.3, p = 0.002).
Conclusion:  The high frequency of novel EV HPV in HPV vulvitis and correlation of clinicopathologic findings with HPV DNA suggests that HPV vulvitis may indeed exist.     

人免疫缺陷病毒阳性人群人乳头状瘤病毒感染的型别分析

目的 了解人免疫缺陷病毒（HIV）阳性人群人乳头状瘤病毒（HPV）感染状况、型别分布特征及与HIV阴性人群的差异。 方法 选择门诊患有尖锐湿疣或主诉近期与可疑尖锐湿疣患者有性接触者作为研究对象,包括HIV阳性组62例和HIV阴性组2 716例,采用基因芯片技术对外生殖器部位皮肤黏膜样本进行HPV检测,采用SPSS 19.0统计软件进行χ2检验。 结果 HIV阳性组中,HPV总感染率74.19%（46/62）,高危型HPV感染率67.74%（42/62）,低危型HPV感染率58.06%（36/62）;HIV阴性组三者感染率分别为42.30%、29.57%、24.71%,两组比较,差异有统计学意义（均P < 0.01）。HIV阳性组男性HPV检出率高达92.11%（35/38）,和HIV阴性组男性检出率相比（37.38%,382/1 022）差异有统计学意义（χ2 = 45.98,P < 0.01）。低危型HPV在HIV阳性组检出率前3位为HPV6（37.10%,23/62）、43和11型,在HPV阴性组检出率排序相同但HPV6的检出率仅11.12%（302/2 716）。高危型HPV在HIV阳性组检出率前5位依次是HPV16（22.58%,14/62）、52、66、58和18型,在HIV阴性组前5位依次为HPV16（7.77%,211/2 716）、58、56、66和52型。HPV亚型重叠感染情况,HIV阳性组最多八重,HIV阴性组最多九重,三重及以上感染者,HIV阳性组65.21%（30/46）,HIV阴性组16.71%（192/1 149）,差异有统计学意义。 结论 HIV阳性人群HPV总感染率、高危型HPV感染率、低危型HPV感染率、男性HPV感染率以及HPV多重感染率均明显高出HIV阴性组,值得临床高度重视。     

P53,CyclinD1和Ki67蛋白在外阴HPV相关疾病中的表达及意义

目的探讨P53,CyclinD1和Ki67蛋白在外阴HPV相关疾病尖锐湿疣、外阴上皮内瘤变、外阴鳞状细胞癌中的表达及意义。方法采用免疫组化SP法检测30例尖锐湿疣;60例外阴上皮内瘤变;20例外阴鳞状细胞癌标本中P53,CyclinD1,Ki67的表达情况,并与10例正常组织进行对照。结果 P53在尖锐湿疣组,外阴上皮内瘤变(VINⅠ级、Ⅱ级、Ⅲ级)组,外阴鳞状细胞癌组,正常组的阳性表达率分别为63.66%,43.48%,52.63%,61.11%,70.00%和0。CyclinD1的阳性表达率分别为43.33%,34.78%,47.37%,55.56%,60.00%和0。Ki67的阳性表达率分别为46.67%,47.83%,57.89%,72.22%,85.00%和0。P53与Ki67蛋白阳性表达呈正相关(P<0.05),Ki67与CyclinD1蛋白阳性表达呈正相关(P<0.05),P53与CyclinD1蛋白阳性表达无相关性(P>0.05)。三者均表达随外阴上皮恶变的进展而增加。结论 P53,CyclinD1和Ki67蛋白在外阴HPV相关疾病的发生,发展中起一定作用。     

外阴HPV相关疾病中p~(53),cyclinD1和ki67蛋白表达及其与HPV感染的关系

目的 探讨人乳头瘤病毒(HPV)在外阴HPV相关疾病—尖锐湿疣(CA)、外阴上皮内瘤变(VIN)和外阴鳞状细胞癌(VSCC)中的感染情况及与p53,cyclinD1,ki67蛋白表达的关系。方法 在110例外阴HPV相关疾病中应用核酸分子快速导流杂交基因分型技术检测HPV16/18,HPV6/11的表达,同时用免疫组化SP法检测p53,cyclinD1,ki67蛋白的表达,并与10例正常组织进行对照。结果 HPV16/18在CA组,VIN组及VSCC组的阳性表达率均高于正常对照组,而且其阳性表达率随外阴上皮恶性程度增加而增加;HPV6/11在CA组及VINⅠ组的阳性表达率均高于VINⅡ组及VINⅢ组和正常对照组;以上差异均有统计学意义(P均<0.05)。HPV6/11在VSCC组无阳性表达,HPV16/18感染与p53,ki67表达呈正相关,与cyclinD1表达无相关性。HPV6/11感染与p53,cyclinD1,ki67表达无相关性。结论 HPV16/18感染与重度外阴上皮内瘤变及外阴鳞状细胞癌密切相关;HPV6/11感染是尖锐湿疣及轻度外阴上皮内瘤变的重要病因。HPV16/18感染与p53,ki67蛋白表达呈正相关,它们在外阴鳞状上皮恶变过程中有着协同的作用。     

外阴鳞状细胞癌中人乳头状瘤病毒感染与基质金属蛋白酶9和金属蛋白酶抑制剂1的关系

目的 探讨人乳头状瘤病毒(HPV)6/11、16/18在外阴鳞状细胞癌(简称外阴鳞癌)组织中的感染情况及与基质金属蛋白酶9(MMP-9)和金属蛋白酶抑制剂1(TIMP-1)蛋白表达的关系.方法 用原位杂交法检测HPV6/11、16/18在26例外阴鳞癌、21例外阴上皮内瘤病变(VIN)及10例外阴正常皮肤组织中的感染情况.同时用免疫组化法检测MMP-9、TIMP-1蛋白的表达.结果 HPV6/11、16/18在外阴鳞癌、VIN中的感染率分别为69.23%(18/26)和38.46%(10/26),42.86%(9/21)和28.57%(6/21),正常对照组没有感染.MMP-9、TIMP-1蛋白在外阴鳞癌、VIN、正常对照组中的阳性表达率分别为92.31%(24/26)和76.92%(20/26),90.48%(19/21)和80.95%(17/21),80.00%(8/10)和50.00%(5/10).HPV6/11的外阴鳞癌组、VIN组与正常对照组比较差异有显著性(P<0.05),HPV16/18的外阴鳞癌组与正常对照组比较差异有显著性.外阴病变各组MMP-9、TIMP-1阳性表达率与正常对照组比较差异均有显著性.在外阴鳞癌中MMP-9蛋白表达较TIMP-1蛋白表达强(P<0.05).MMP-9在有HPV6/11和HPV16/18感染患者中的表达较无感染者强,而TIMP-1蛋白的表达差异无显著性.结论 在外阴鳞癌的发生发展中HPV的感染起一定作用,当MMP-9的表达强于TIMP-1表达时可能是外阴鳞癌侵袭的一个指标,HPV感染可能会进     

Altered clinical course of malignant melanoma in HIV-positive patients

OBJECTIVE: To determine whether the natural history of melanoma is different in patients who test positive for human immunodeficiency virus (HIV) compared with matched control subjects. DESIGN: Retrospective cohort analysis. SETTING: Ambulatory care at 2 university-affiliated medical centers. PATIENTS: Each HIV-positive melanoma patient (n = 17) was randomly matched with 2 HIV-negative patients (HIV status unknown, but without risk factors for HIV) based on the melanoma subtype, tumor thickness, Clark level, tumor location, and sex and age of the patient. MAIN OUTCOME MEASURES: Disease-free survival and overall survival of HIV-positive and HIV-negative melanoma patients were compared using a matched-pairs analysis. CD4 cell counts were recorded at the time of melanoma diagnosis and disease recurrence. RESULTS: Melanoma patients who were HIV positive had a significantly shorter disease-free survival (P =.03) and overall survival (P =.045) compared with HIV-negative melanoma patients by matched-pairs analysis. There was an inverse relationship between CD4 cell counts and time to first melanoma recurrence. CONCLUSIONS: The natural history of malignant melanoma in HIV-positive patients is more aggressive compared with matched HIV-negative melanoma patients. Altered immune response and comorbid disease may play a role in the poor clinical outcome of HIV-positive patients. These findings have important implications in the management of melanoma in the setting of HIV disease.     

Human papillomavirus infection in men who have sex with men participating in a Dutch gay-cohort study

BACKGROUND: To develop strategies for prevention and early treatment of human papillomavirus (HPV) anal and penile cancer, a better understanding of related sexual behavior risk factors is needed. GOAL: The goal of this study was to establish the prevalence of anal and coronal sulcus HPV in a group of men who have sex with men participating in a Dutch gay-cohort study, to identify risk factors associated with HPV infection in this group, and to investigate the presence of identical HPV types in couples with stable relationships. STUDY DESIGN: A cross-sectional study of 241 HIV-negative and 17 HIV-positive men who have sex with men visiting the sexually transmitted disease clinic of the Erasmus MC for a regular and scheduled examination. Participants underwent a routine venereological examination including HIV serologic analysis, and swabs were taken from the coronal sulcus and anus for HPV DNA testing. All subjects were asked to complete a questionnaire on sexual risk behavior. RESULTS: HPV DNA was detected at the coronal sulcus in 23.5% of the HIV-positive men and in 15.8% of the HIV-negative men (P=0.492). In anal specimens, HPV DNA was detected in 64.7% of the HIV-positive men and 32.8% of the HIV-negative men (P=0.015). High-risk HPV types (P=0.007) and 2 or more different HPV genotypes (P=0.006) were seen more often in anal specimens of HIV-positive persons than in specimens of HIV-negative persons. A factor possibly associated with the presence of anal HPV infection was a concomitant anal infection with Chlamydia trachomatis, gonococci, or herpes simplex virus (P=0.059). In only 16.7% of HPV-positive steady couples, both companions showed the presence of one or more identical HPV genotypes. CONCLUSION: In this study, anal HPV DNA was detected more often than HPV DNA at the coronal sulcus. HIV positivity was associated with a higher prevalence of high-risk, but not with low-risk HPV types, at the anus. No association was found between HIV positivity and presence of high-risk HPV at the coronal sulcus. No sexual behavioral determinants for the presence of HPV could be identified. Concomitant anal infection with C trachomatis, gonococci, or herpes simplex virus may be associated with HPV infection. In the majority of steady couples, partners were infected with different HPV types.     

The under-reporting of skin disease in association with squamous cell carcinoma of the vulva

Histology sections from 61 cases of squamous cell carcinoma (SCC) of the vulva presenting alter 1988 were reviewed for evidence of associated epithelial abnormality. Of the 50 patients with epithelium adjacent to the tumour, 24 had histological evidence of lichen sclerosus (LS), 20 of severe vulvar intraepithelial neoplasia (VIN 3), 22 of human papilloma virus (HPV) infection and three of lichen planus (LP). The clinical records and the original histology report were also subsequently reviewed and with the exception of VIN 3, these disorders were poorly reported by both clinicians and pathologists. Lichen sclerosus was diagnosed clinically in only two of the 36 hospital records available for inspection. Old terminology was used to describe some patients with epithelial disease (erythroleueoplakia in one patient with LS, leucoplakia in two patients with LS and one with LP). This study demonstrates the need to adopt standard nomenclature and increase the awareness of epithelial disease associated with SCC of the vulva among clinicians and pathologists.     

深圳地区女性HIV合并宫颈HPV感染现状调查及临床干预的相关性研究

目的探究深圳地区女性HIV合并宫颈HPV感染的现状及临床干预效果。方法以2017年1月1日至2018年2月1日期间在广东省深圳市第三人民医院爱心门诊就诊、HIV阳性的女性作为研究对象。随机选取同期在广东省深圳市第三人民医院妇科门诊行宫颈癌筛查的HIV阴性女性作为对照,两组各选550例,对所有研究对象均行宫颈相关检测、免疫细胞和HIV病毒载量测定,统计HPV感染现状,对HPV感染率与CD4^+水平与HIV病毒RNA定量相关性进行分析。将HIV阳性合并感染HR-HPV的患者分为两组,一组采用抗HIV病毒治疗,另一组不进行任何治疗,对HIV阴性但HPV感染阳性的患者分为四组,A组采用重组人干扰素a2b乳膏+保妇康栓治疗,B组采用阴道干扰凝胶治疗,C组采用阴道保妇康栓治疗,D组不给于任何治疗,3疗程后,分别在停药后3个月、6个月、12个月对患者进行HPV定性及定量检查和LCT检测,评估疗效差别。结果 HIV阳性患者的HPV感染率、HR-HPV感染率、多重HPV感染、细胞学异常发生率和其他阴道疾病感染率显著高于HIV阴性患者,同时HIV阳性组的宫颈病变率和病变分期与HIV阴性患者组别之间存在显著的统计学差异(均P<0.05);HIV阳性合并HR-HPV感染组的CD4^+细胞数和CD4^+/CD8^+显著低于未合并HR-HPV感染组, HIV病毒载量显著高于未合并HR-HPV感染组,差异均具有统计学意义(均P<0.05);A组的好转率优于其他三组,B组和C组的好转率优于D组,均存在统计学差异(均P<0.05);在HIV阳性合并HR-HPV中采用抗病毒治疗组在术后的3个月、6个月、12个月的HR-HPV感染率、多重感染、自然转归细胞学异常均显著优于未抗HIV治疗组别,差异均具有统计学意义(均P<0.05)。结论 HIV病毒感染能够增加HR-HPV的感染机率,在此类患者的治疗上应该增加抗病毒治疗,同时在HPV感染的治疗上应该提倡联合用药的方式,对于疾病的转归具有重要意义。     

Treatment of undifferentiated vulvar intraepithelial neoplasia with 5% imiquimod cream: a prospective study of 12 cases

OBJECTIVE: To assess the efficacy of 5% imiquimod cream on undifferentiated vulvar intraepithelial neoplasia (VIN), a disease caused by high-risk human papillomavirus. DESIGN: Prospective, uncontrolled study. SETTING: University hospital vulvar clinic.Patients Twelve consecutive patients treated with 5% imiquimod cream for undifferentiated VIN between March 1, 1999, and May 31, 2001. INTERVENTION: Self-application of 5% imiquimod cream, initially 3 times a week, then adjusted according to tolerance, for up to 7 months according to clinical response. MAIN OUTCOME MEASURES: Therapeutic response, clinically assessed by successive photographs and histologically confirmed for complete responders, was scored as complete, partial (> or =50% decrease in lesion size), or failure. Tolerance was evaluated at each visit. RESULTS: A total of 3, 4, and 5 patients achieved complete response, partial response (> or =75% reduction in lesion size for all such cases), and failure, respectively. Mean duration of treatment was 3.6 months (37.3 applications), 5.0 months (50.7 applications), and 3.4 months (25.2 applications) for complete responders, partial responders, and failures, respectively. Follow-up after treatment was 5 to 18, 14 to 32, and 2 to 28 months, respectively, with 1 partial responder lost to long-term follow-up. No patient developed invasive carcinoma. All but 2 patients experienced vulvar discomfort, resulting in treatment withdrawal for 3. Two patients had flulike symptoms. CONCLUSIONS: Imiquimod cream could be a therapeutic option for undifferentiated VIN. Although poorly tolerated, this self-applied treatment could spare patients, either totally or partially, the classic painful and sometimes mutilating treatments of VIN. Controlled, randomized studies are needed to evaluate its efficacy and tolerance.     

Similar serological response to conventional therapy for syphilis among HIV-positive and HIV-negative women.

OBJECTIVES--To compare characteristics of syphilis serological reactivity in HIV positive (+) and HIV negative (-) female sex workers, as well as the serological response to therapy after treatment with intramuscular benzathine penicillin, 2.4 million U weekly, for three consecutive weeks. METHODS--Rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) results of 72 HIV-positive and 121 HIV-negative women reactive in both tests were assessed. The response to therapy was prospectively monitored with quantitative RPR serology in 47 HIV-positive and 73 HIV-negative patients. Cumulative probabilities of becoming nonreactive by RPR were compared at six months, one and two years after therapy. RESULTS--At enrolment, the geometric mean titres of RPR and TPHA were lower in HIV-positive patients (RPR, 1:2.6) than in HIV-negative patients (RPR, 1:3.8; p < 0.01). The evolution over time of RPR titres was similar among HIV-positive patients as compared to HIV-negative patients. Among patients with an initial RPR titre of < 1:8, 53% of HIV-positive and 44% of HIV-negative patients became RPR negative two years after therapy. Among patients with an RPR titre of 1:8 or greater at enrolment, 83% of HIV-positive and 90% of HIV-negative patients had reached at least a fourfold decline of RPR titres two years after therapy. CONCLUSIONS--Syphilis serology findings (both RPR and TPHA) may be altered in the presence of HIV infection, but the serological response to therapy was similar in HIV-positive and HIV-negative patients.